Use of Almitrine and Inhaled Nitric Oxide in ARDS Due to COVID-19

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial dysfunction leading to particularly severe hypoxemia. We hypothesized that an impaired hypoxic pulmonary vasoconstriction aggravates hypoxemia. The objective of the study was to test the effect of two pulmonary vasoactive drugs on patient oxygenation.Methods: Observational, single-center, open-label study in one intensive care unit (ICU) of the Paris area, realized in April 2020. Eligible patients had coronavirus disease 2019 (COVID-19) and moderate to severe ARDS [arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <200 mmHg] despite conventional protective ventilation. Exclusion criteria included pulmonary artery hypertension defined by a pulmonary artery systolic pressure (PAPs) >45 mmHg. The assessment of oxygenation was based on PaO2/FiO2 at (1) baseline, then after (2) 30 min of inhaled nitric oxide (iNO) 10 ppm alone, then (3) 30 min combination of iNO + almitrine infusion 8 μg/kg/min, then (4) 30 min of almitrine infusion alone.Results: Among 20 patients requiring mechanical ventilation during the study period, 12 met the inclusion criteria. Baseline PaO2/FiO2 was 146 ± 48 mmHg. When iNO was combined with almitrine, PaO2/FiO2 rose to 255 ± 90 mmHg (+80 ± 49%, p = 0.005), also after almitrine alone: 238 ± 98 mmHg (+67 ± 75%, p = 0.02), but not after iNO alone: 185 ± 73 mmHg (+30 ± 5%, p = 0.49). No adverse events related to almitrine infusion or iNO was observed.Conclusion: Combining iNO and infused almitrine improved the short-term oxygenation in patients with COVID-19-related ARDS. This combination may be of interest when first-line therapies fail to restore adequate oxygenation. These findings argue for an impaired pulmonary hypoxic vasoconstriction in these patients.

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Sildenafil therapy for neonatal and childhood pulmonary hypertensive vascular disease

Cardiology in the Young ◽

10.1017/s1047951110001745 ◽

2010 ◽

Vol 21 (2) ◽

pp. 187-193 ◽

Cited By ~ 28

Author(s):

Tilman Humpl ◽

Janette T. Reyes ◽

Simon Erickson ◽

Ruth Armano ◽

Helen Holtby ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Right Ventricular ◽

Pressure Ratio ◽

Systolic Pressure ◽

Resistance Index ◽

Pulmonary Artery Hypertension ◽

Inhaled Nitric Oxide ◽

Drug Study

AbstractObjectivesWe hypothesised that sildenafil would improve hemodynamics in children with pulmonary hypertension and attenuate rebound pulmonary hypertension after inhaled nitric oxide withdrawal.Patients and methodsWe undertook an open-label, single-drug study of sildenafil in patients under 5 years of age with either symptomatic or rebound pulmonary hypertension following inhaled nitric oxide withdrawal.ResultsWe recruited 25 patients (median age 180 days, 10–1790) to receive sildenafil. The median right ventricular to systemic systolic blood pressure ratio before sildenafil therapy was 1.0 (0.5–1.4) and decreased to 0.5 (with a range from 0.3 to 1.3; p = 0.0002). In five patients the baseline pulmonary vascular resistance index was 10 (7.1–13.6) Wood units metre square and decreased to 5.8 (2.7–15.6) Wood units metre square (p = 0.04) at 6 months. Ten patients were treated with sildenafil for a median of 34 days (9–499) until resolution of pulmonary artery hypertension and continue to do well. Six patients continued sildenafil therapy for a median of 1002 days (384–1574) with improvement but without resolution of pulmonary hypertension. There was no change in serum creatinine, urea, liver function tests, or platelet count. In 15 patients sildenafil abolished rebound pulmonary artery hypertension following withdrawal of inhaled nitric oxide. Median right ventricular pressure to systemic systolic pressure ratio decreased from 1.0 (0.8–1.4) during nitric oxide withdrawal to 0.4 (0.3–0.8) p = 0.006 after pre-treatment with sildenafil.ConclusionIn children under 5 years of age with severe pulmonary hypertension, sildenafil therapy resulted in prolonged hemodynamic improvements without adverse effects. Sildenafil attenuated rebound pulmonary hypertension after withdrawal of inhaled nitric oxide.

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The response to inhaled nitric oxide in patients with pulmonary artery hypertension is not masked by baseline vasodilator use

American Heart Journal ◽

10.1016/j.ahj.2004.10.012 ◽

2005 ◽

Vol 150 (4) ◽

pp. 725-728 ◽

Cited By ~ 5

Author(s):

Richard A. Krasuski ◽

Andrew Wang ◽

J. Kevin Harrison ◽

Victor F. Tapson ◽

Thomas M. Bashore

Keyword(s):

Nitric Oxide ◽

Pulmonary Artery ◽

Pulmonary Artery Hypertension ◽

Inhaled Nitric Oxide

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Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders

Journal of Applied Physiology ◽

10.1152/japplphysiol.00205.2005 ◽

2005 ◽

Vol 99 (5) ◽

pp. 1796-1801 ◽

Cited By ~ 76

Author(s):

Brian D. Hoit ◽

Nancy D. Dalton ◽

Serpil C. Erzurum ◽

Daniel Laskowski ◽

Kingman P. Strohl ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Pulmonary Artery ◽

High Altitude ◽

Sea Level ◽

Pulmonary Blood Flow ◽

Geometric Mean ◽

Systolic Pressure ◽

Pulmonary Artery Systolic Pressure ◽

Exhaled No

When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 ± 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 ± 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure.

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Assessment of pulmonary artery hypertension by Doppler echocardiography and its correlation with right heart catheterization

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20211049 ◽

2021 ◽

Vol 8 (4) ◽

pp. 523

Author(s):

Vikrant B. Khese ◽

Chandrakant B. Chavan ◽

Ravi Kalra ◽

Anirudh K. Allam ◽

Abhinav Mohabey

Keyword(s):

Pulmonary Artery ◽

Systolic Pressure ◽

Maximum Velocity ◽

Right Heart Catheterization ◽

Pulmonary Artery Hypertension ◽

Pulmonary Artery Systolic Pressure ◽

Heart Catheterization ◽

Right Heart ◽

Number Of Patients ◽

Pulmonary Arterial

Background: Definitive diagnosis of pulmonary artery hypertension (PH) requires an elevated mean pulmonary arterial pressure (MPAP) of 25 mmHg at rest measured by right heart catheterization (RHC). As it is invasive mode of investigation, it is declined by many patients, echocardiography was thought to be an acceptable substitute to assess pulmonary arterial pressures. Whether there is a correlation between these measurements is controversial. The aim of this study was to assess PH by echocardiography and its correlation with RHC.Methods: Twenty-six patients aged ≥18 years with pulmonary artery hypertension with or without tricuspid regurgitation (TR) were included in this cross-sectional study. All the patients underwent a transthoracic echocardiography evaluation and were taken for RHC study within an hour.Results: The correlation between pulmonary artery acceleration time (PAAT) and pulmonary artery systolic pressure (PASP) and PAAT and MPAP was significant in all degrees of PH. In contrast, correlation between TR jet maximum velocity (TR Vmax) derived estimated pulmonary artery systolic pressure (EPASP) and PASP was significant in moderate and severe PH, while it did not correlate in mild PH.Conclusions: PAAT is easily measurable parameter and strongly correlates with the values of PASP and the MPAP obtained by right heart catheterization. Implementation of a novel method of determining EPASP from PAAT shall increase significantly the number of patients in whom TTE can be used for the assessment of pulmonary hemodynamic non-invasively.

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Clinical value of noninvasive pulmonary artery systolic pressure estimates in our patients with pulmonary artery hypertension

Critical Care ◽

10.1186/cc7395 ◽

2009 ◽

Vol 13 (Suppl 1) ◽

pp. P231

Author(s):

T Šubic ◽

I Drinovec ◽

F Šifrer

Keyword(s):

Pulmonary Artery ◽

Systolic Pressure ◽

Pulmonary Artery Hypertension ◽

Pulmonary Artery Systolic Pressure ◽

Clinical Value

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Inhaled nitric oxide for treatment of pulmonary artery hypertension in the newborn and infant

Critical Care Medicine ◽

10.1097/00003246-199309001-00047 ◽

1993 ◽

Vol 21 (Supplement) ◽

pp. S374-S375 ◽

Cited By ~ 16

Author(s):

JESSE D. ROBERTS

Keyword(s):

Nitric Oxide ◽

Pulmonary Artery ◽

Pulmonary Artery Hypertension ◽

Inhaled Nitric Oxide

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Secondary Pulmonary Hypertension and Right-Sided Heart Failure at Presentation in Grave’s Disease

Case Reports in Endocrinology ◽

10.1155/2012/762023 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3

Author(s):

Swapnil Panjabrao Ganeshpure ◽

Gaurang Nandkishor Vaidya ◽

Vipul Gattani

Keyword(s):

Heart Failure ◽

Pulmonary Artery ◽

Systolic Pressure ◽

Pulmonary Artery Hypertension ◽

Left Ventricular ◽

Pulmonary Vasculature ◽

Pulmonary Artery Systolic Pressure ◽

Thyroid Function Tests ◽

Grave’S Disease ◽

Grave's Disease

A young female presented with evidence of right-sided heart failure and was subsequently found to have significant pulmonary artery hypertension (PAH). Because of her normal left ventricular function and pulmonary capillary wedge pressure, the most probable site of etiology seemed to be the pulmonary vasculature. All the common possible secondary causes of PAH were ruled out, but during the investigations, she was found to have elevated thyroid function tests compatible with the diagnosis of Grave’s disease. The treatment of Grave’s disease, initially by medications and subsequently by radioiodine therapy, was associated with a significant reduction in the pulmonary artery systolic pressure. The purpose of this case report is to highlight one of the unusual and underdiagnosed presentations of Grave’s disease.

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Endothelial Nitric Oxide Synthase Polymorphisms Do Not Influence Pulmonary Artery Systolic Pressure at Altitude

High Altitude Medicine & Biology ◽

10.1089/ham.2006.7.221 ◽

2006 ◽

Vol 7 (3) ◽

pp. 221-227 ◽

Cited By ~ 11

Author(s):

Eve M.D. Smith ◽

J. Kenneth Baillie ◽

A.A. Roger Thompson ◽

John B. Irving ◽

David Porteous ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Pulmonary Artery ◽

Endothelial Nitric Oxide Synthase ◽

Systolic Pressure ◽

Pulmonary Artery Systolic Pressure ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Inhaled nitric oxide therapy for adult respiratory distress syndrome

Critical Care Nurse ◽

10.4037/ccn1998.18.6.21 ◽

1998 ◽

Vol 18 (6) ◽

pp. 21-27 ◽

Cited By ~ 3

Author(s):

CH Burke-Martindale

Keyword(s):

Nitric Oxide ◽

Pulmonary Artery ◽

Oxygen Toxicity ◽

Concomitant Administration ◽

Pulmonary Artery Hypertension ◽

Inhaled Nitric Oxide ◽

Pulmonary Barotrauma ◽

Safe Delivery ◽

Nitric Oxide Therapy ◽

The Impact

The selective pulmonary vasodilatory effects of inhaled nitric oxide decrease pulmonary artery hypertension and improve arterial oxygenation in patients with ARDS without causing concomitant systemic vasodilation. Inhaled nitrix oxide therapy may decrease the prevalence of pulmonary edema, pulmonary barotrauma, and oxygen toxicity that occur with current ARDS treatment. The effect of nitric oxide on oxygenation and pulmonary artery pressure may allow more time for the lungs to recover. Initial results of clinical trials are encouraging; however, the impact of inhaled nitric oxide therapy on patients with ARDS remains unclear. Further research is needed to develop safe delivery systems and monitoring techniques for routine clinical use, to determine potential adverse and toxic effects of nitric oxide therapy on patients, and to determine the effects of long-term exposure to nitric oxide among healthcare workers. Concomitant administration of other medications with inhaled nitric oxide should also be investigated.

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